The overall objective of the Neurobiology Core is to provide the HNRC and NeuroAIDS-associated investigators with a set of neuropathological technical and in vivo and in vitro neurobiological resources that will allow for the analysis of the neurodegenerative processes associated with prolonged survival with HIV infection from a comprehensive and dynamic perspective. During the previous period of funding we developed several collaborations and provided support to over 20 funded investigators in the neuroAIDS field. Specifically for the renewal we will provide: 1) an array of techniques to facilitate quantitative analysis of neuronal injury that will facilitate studies on HIV-mediated neuropathogenesis;2) technical assistance and consultation on state-of-the-art neuropathological approaches;3) support preliminary studies that utilize neuropathology data;4) mentorship for students and junior faculty in neurobiology and neuropathology;5) Collaborate with the Coordinating Core to disseminate information on HIV-related neuropathology and 6) technical support and facilitate the establishment of international collaborations. In anticipation of current and future needs derived from such investigations, we will expand our studies of neurodegeneration to include dendritic spine analysis in luciferase yellow-filled neurons, analysis of neurogenesis and white matter damage, establishing HIV-infected mixed neuronal cultures, and providing a flexible infrastructure for novel and more sensitive 3-D reconstruction techniques between neuropathological and neuroimaging studies. Understanding the neuropathological basis for variants of neuroAIDS that have emerged in the era of HAART will help elucidate the mechanisms through which HIV infection leads to cognitive dysfunction and to point to new treatment strategies for neuroAIDS. Collaborative capacity building in resource limited settings will help research into possibly altered HIV neuropathogenesis related to viral and host differences in international settings.